Dinuclear copper catalyst for the oxidation/oxygenation of hydrocarbons

ABSTRACT

The subject invention provides synthetic compounds, and compound complexes having catalytic activities towards oxidation or oxygenation, and/or dehydrogenation of various substrates comprising C—H bonds. The catalysts of the subject invention comprise a dinuclear Cu(I)/Cu(II) center that can convert between a resting state and a reactive species. The subject invention also provides methods of using such catalysts for the oxidation of substrates comprising C—H bonds, e.g., hydrocarbons, to synthesize chemicals for use as pharmaceuticals and industrial feedstock.

CROSS-REFERENCE TO A RELATED APPLICATION

This application is a continuation application of U.S. Ser. No.17/159,519, filed Jan. 27, 2021, which is incorporated herein byreference in its entirety.

BACKGROUND OF THE INVENTION

Copper plays a wide variety of roles in, for example, electron transfer(ET), O₂ binding, activation and reduction, and substrate activation dueto its accessible I/II redox couple and bioavailability. One property ofCu is the existence in either a reduced, Cu⁺, or oxidized, Cu²⁺, state.Since Cu⁺ has an affinity for thiol and thioether groups while Cu²⁺exhibits preferred coordination to oxygen or imidazole nitrogen groups,such metal ion can participate in a wide spectrum of interactions withproteins to drive diverse structures and biochemical reactions.

Metalloproteins are important proteins that include a metal center, suchas Fe, Ca, Cu or Zn, and a protein structure, typically composed ofelements such as carbon, nitrogen, oxygen, hydrogen and sulfur,surrounding the metal center. The metal center may contain one or moremetal atoms. Dinuclear copper assemblies are encountered in the activecenters of various metalloproteins, such as hemocyanin, tyrosinase,catechol oxidase, laccase and particulate methane monooxygenase (pMMO).

The dinuclear copper center can catalyze intricate chemical reactions ofbiological importance. For example, pMMO catalyzes the conversion ofmethane to methanol. The role of the protein backbone in thesemetalloproteins is to hold the two Cu-centers together in a mannerallowing them to reach close proximity upon two-electron oxidation ofthe Cu(I) rest state to the Cu(II) catalytically active form. Forexample, in catechol oxidase, the distance between two Cu(I) is 4.4 Åwhile the distance between two Cu(II) is 2.5 Å.

There has been an interest to produce synthetic catalysts that can bringthe two copper centers together to mimic the functionality of thoseCu-containing proteins. Redox and magnetic properties are also majorresearch foci of dicopper chemistry. Thus, it is desired to developand/or synthesize copper-containing complexes for catalyzing crucialconversions of biological or industrial importance, by facilitatingvarious C—H activation reactions, e.g., oxidizing sp³-hybridized C—Hbonds.

Further, the oxidation/oxygenation of hydrocarbons has been recognizedto play a role in infectious and neurodegenerative diseases. Thus, thereis also a need to develop and/or synthesize copper-containing catalystsfor producing specific chemicals for pharmaceutical and industrialapplications.

BRIEF SUMMARY OF THE INVENTION

The subject invention provides synthetic copper-containing complexeshaving catalytic activities towards oxidation or oxygenation, and/ordehydrogenation of various substrates comprising C—H bonds, andcompositions comprising such copper-containing complexes. Thecopper-containing complexes comprise one or more copper atoms that canconvert between a resting state (a reduced oxidation state) and acatalytically-active state (oxidized state), thereby recycling thereactive species for the subsequent catalytic cycles.

In one embodiment, the substrates comprising C—H bonds are hydrocarbons.In a further embodiment, the hydrocarbons are selected from straight,branched, cyclic, saturated or unsaturated alkanes, alkenes, alkynes,heterocycles, aromatics and polymeric compounds.

In one embodiment, the subject invention provides a copper-containingcatalyst comprising a dinuclear copper complex that comprises acopper-containing compound having a bi-copper center joined by bidentateor multidentate ligands, and optionally, the dinuclear copper complexcomprising a stabilizing counter ion. In a further embodiment, thebi-copper center comprises a μ-OH that can form a hydrogen bond with thestabilizing counter ion. The bidentate or multidentate ligands and thestabilizing counter ion may be the same or different.

The dinuclear copper complex shows catalytic activity towards oxidationor oxygenation of substrates comprising at least one C—H bond, e.g.,hydrocarbons, and cycle between a Cu(II)—OH—Cu(II) form and aCu(I)—Cu(I) resting state, as follows: the Cu(I)—Cu(I) resting state ofthe dinuclear copper complex is oxidized by, for example, atmosphericoxygen, or other reactive species to form a Cu(II)—OH—Cu(II) species.The latter reacts with substrates comprising at least one C—H bond,e.g., hydrocarbons, either dehydrogenating them with formation of H₂O,or oxygenating them by adding its O-atom to the substrate. Upon reactionwith the substrates, e.g., hydrocarbons, the complex returns to theCu(I)—Cu(I) state, closing the catalytic cycle. While the copper complexis in its rest Cu(I)13 Cu(I) state, the H-atom of Cu(II)—OH—Cu(II) isbound to the counter ion (neutralizing its charge), from where it isshuttled back to the complex upon re-oxidation.

In one embodiment, the subject invention provides a dinuclear coppercatalyst comprising a dinuclear copper complex and a stabilizing counterion, wherein the dinuclear copper complex cycles between a restingdinuclear Cu(I) complex and a catalytic dinuclear Cu(II) complex, thecatalytic dinuclear Cu(II) complex comprising a Cu(II)—OH—Cu(II) center.

Advantageously, the synthesis of the dinuclear copper catalyst of thesubject invention is cost-effective, which makes the production ofspecific chemicals using such dinuclear copper catalyst inexpensive.Also, value may be added to low grade hydrocarbons that can be used assubstrates of the dinuclear copper catalyst.

In one embodiment, the resting dinuclear Cu(I) complex has a generalstructure of the formula (A):

wherein

represents a peripheral chelating ligand substitution, preferably,

is

and wherein R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″, R₃″, R₄″, R₅″,R₆″, R₂″′, R₃″′, R₄′″, R₅′″, and R₆′″ are each independently selectedfrom the group consisting of hydrogen, —COOH, —NO₂, alkyl, substitutedalkyl, aryl, substituted aryl, heteroalkyl, substituted heteroalkyl,heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl,heterocycloalkyl, substituted heterocycloalkyl, cycloalkenyl,substituted cycloalkenyl, alkenyl, substituted alkenyl, alkynyl, alkoxy,substituted alkoxy, acyl, carboxyalkyl, halogen, amino, substitutedamino, hydroxyl, hydroxylalkyl, and substituted hydroxylalkyl.

In one embodiment, the catalytic dinuclear Cu(II) complex has a generalstructure of the formula (B):

wherein

represents a peripheral chelating ligand substitution, preferably,

is

and wherein R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″, R₃″, R₄″, R₅″,R₆″, R₂″′, R₃″′, R₄″′, R₅″′, and R₆′″ are each independently selectedfrom the group consisting of hydrogen, —COOH, —NO₂, alkyl, substitutedalkyl, aryl, substituted aryl, heteroalkyl, substituted heteroalkyl,heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl,heterocycloalkyl, substituted heterocycloalkyl, cycloalkenyl,substituted cycloalkenyl, alkenyl, substituted alkenyl, alkynyl, alkoxy,substituted alkoxy, acyl, carboxyalkyl, halogen, amino, substitutedamino, hydroxyl, hydroxylalkyl, and substituted hydroxylalkyl.

In one embodiment, the dinuclear copper catalyst comprises a stabilizingfree ligand as counterion, whose ionic form has a general structure of

that can form a hydrogen bond with the μ-OH of the dinuclear Cu(II)complex, while the neutral form of the free ligand has a general

structure of

wherein R₁, R₂″, R₃″, R₄″, R₅″, R₆″, R₂′″, R₃′″, R₄″′, R₅′″, and R₆′″are each independently selected from the group consisting of hydrogen,—COOH, —NO₂, alkyl, substituted alkyl, aryl, substituted aryl,heteroalkyl, substituted heteroalkyl, heteroaryl, substitutedheteroaryl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl,substituted heterocycloalkyl, cycloalkenyl, substituted cycloalkenyl,alkenyl, substituted alkenyl, alkynyl, alkoxy, substituted alkoxy, acyl,carboxyalkyl, halogen, amino, substituted amino, hydroxyl,hydroxylalkyl, and substituted hydroxylalkyl.

The subject invention further provides methods for using the dinuclearcopper catalyst for the oxidation of substrates comprising C—H bonds,including dehydrogenation and oxygenation of substrates comprising C—Hbonds.

In one embodiment, the subject invention provides a method for oxidizingor oxygenating a hydrocarbon comprising contacting, combining, and/ormixing the dinuclear copper catalyst of the subject invention with thehydrocarbon.

In one embodiment, the subject invention provides a method for formingan alcohol, an aldehyde, an alkene or an aromatic from a hydrocarbon,the method comprising contacting, combining, and/or mixing thehydrocarbon with the dinuclear copper catalyst of the subject invention.In a further embodiment, the alcohol is a primary alcohol, a secondaryalcohol, or a tertiary alcohol.

In certain embodiments, the hydrocarbon is selected from alkanes,alkenes, alkynes, aromatics and polymeric compounds. In specificembodiments, the hydrocarbon is selected from dihydroanthracene (DHA),toluene, tetrahydrofuran (THF), 2,2,4-trimethylpentane,methylcyclohexane, methane, cyclopropane, cyclobutane, cyclopentane,cyclohexane and polyethylene.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

FIG. 1 shows the ball-and-stick diagram ofCu(II)₂(μ-OH)(μ-pnpz)₂(η²-2,2′-bipy)₂. The hydrogen atoms andpentanitropyrazole (pnpz⁻) anion are not shown for clarity. Color code:Cu, blue; O, red; N, light blue; C, black.

FIG. 2 shows the scheme of Cu(II)₂(μ-OH) catalyzing dihydroanthracene toanthracene. A hydrogen bond is formed between the hydrogen of (μ-OH) andpnpz⁻ anion.

FIG. 3 shows the scheme of Cu(II)₂(μ-OH) catalyzing toluene to benzylalcohol and benzaldehyde. A hydrogen bond is formed between the hydrogenof (μ-OH) and pnpz⁻ anion.

DETAILED DESCRIPTION OF THE INVENTION

The subject invention provides synthetic copper-containing complexeshaving catalytic activities towards oxidation or oxygenation, and/ordehydrogenation of various substrates comprising C—H bonds. Suchcopper-containing complexes comprise one or more copper atoms that canconvert between a resting state (a reduced oxidation state) and acatalytically-active state (oxidized state), thereby recycling thereactive species for subsequent catalytic cycles.

In one embodiment, the substrates comprising C—H bonds are hydrocarbons.In a further embodiment, the hydrocarbons are selected from straight,branched, cyclic, saturated or unsaturated alkanes, alkenes, alkynes,heterocycles, aromatics and polymeric compounds.

The subject invention provides compositions comprising thecopper-containing complexes. The subject invention also provides methodsfor using such copper-containing complexes for the oxidation ofsubstrates comprising C—H bonds, including dehydrogenation andoxygenation of substrates comprising C—H bonds. Upon reacting withsubstrates comprising C—H bonds, e.g., hydrocarbons, thecooper-containing complexes returns to the resting state, closing thecatalytic cycle.

In one embodiment, the subject invention provides a copper-containingcatalyst comprising a copper-containing compound having one or morecopper centers complexed with one or more bidentate or multidentateligands and, optionally, a stabilizing ligand or counter ion, whereinthe copper centers comprise a μ-OH that forms a hydrogen bond with thestabilizing ligand or counter ion.

In a preferred embodiment, the copper-containing catalyst comprises adinuclear copper complex comprising a copper-containing compound havinga bi-copper center joined by bidentate or multidentate ligands and,optionally, a stabilizing ligand or counter ion, wherein the bi-coppercenter comprises a μ-OH that forms a hydrogen bond with the stabilizingligand or counter ion. The bidentate or multidentate ligands and thestabilizing ligand or counter ion may be the same or different.

DEFINITIONS

As used herein, the term “hydrocarbon” refers to any molecule havingcarbon and hydrogen in any combination. “Hydrocarbon” includesstraight-chain, branched, cyclic, saturated or unsaturated alkanes,alkenes, alkynes, heterocycles, aromatics and polymeric compounds.

The term “alkane” refers to any saturated hydrocarbon. “Alkane” mayinclude straight-chain, branched, and cyclic alkanes (includingmonocyclic and polycyclic alkanes). The straight-chain or branchedalkanes may have a general formula of C_(n)H_(2n+2). The monocyclicalkanes may have a general formula of C_(n)H_(2n). Examples include, butare not limited to, methane, ethane, propane, butane, pentane, hexane,heptane, octane, nonane, decane, undecane, dodecane, tridecane,tetradecane, pentadecane, hexadecane, heptadecane, octadecane,nonadecane, icosane, triacontane, cyclopropane, cyclobutane,cyclopentane, cyclohexane, cycloheptane, cyclooctane, and the like.

The term “alkene” refers to any hydrocarbon that contains one or morecarbon-carbon double bonds. “Alkene” may include straight-chain,branched, and cyclic alkenes (including monocyclic and polycyclicalkenes). Examples include, but are not limited to, ethane, propene,butene, pentane, hexene, heptene, octene, nonene, decene, dodecene,propadiene, butadiene, pentadiene, hexadiene, octadiene, and the like.

The term “alkyne” refers to any hydrocarbon that contains one or morecarbon-carbon triple bonds. “Alkyne” may include straight-chain,branched, and cyclic alkynes. Those with one triple bond have a generalformula of C_(n)H_(2n−2). Examples include, but are not limited to,ethyne, propyne, butyne, pentyne, hexyne, heptyne, octyne, nonyne,decyne, and the like.

The term “aromatic hydrocarbon,” also known as arene, refers to anyhydrocarbon that has at least one aromatic ring.

As used herein, “alkyl” means saturated monovalent radicals of at leastone carbon atom or a branched saturated monovalent of at least threecarbon atoms. It may include straight-chain alkyl groups, branched-chainalkyl groups, cycloalkyl (alicyclic) groups, alkyl substitutedcycloalkyl groups, and cycloalkyl substituted alkyl groups. It mayinclude hydrocarbon radicals of at least one carbon atom, which may belinear. Examples include, but are not limited to, methyl, ethyl, propyl,2-propyl, n-butyl, iso-butyl, tert-butyl, pentyl, hexyl, and the like.

As used herein, “acyl” means a group —C(O)R where R includes, but is notlimited to, hydrogen, alkyl or cycloalkyl, and heterocycloalkyl.Examples include, but are not limited to, formyl, acetyl, ethylcarbonyl,and the like. An aryl group may be substituted or unsubstituted.

As used herein, the terms “alkoxyl” or “alkoxy” refer to an alkyl group,as defined above, having an oxygen radical attached thereto. Examplesinclude, but are not limited to, methoxy, ethoxy, propyloxy, tert-butoxyand the like.

As used herein, “carboxyalkyl” means a group —COOR where R includes, butis not limited to, hydrogen, alkyl or cycloalkyl, and heterocycloalkyl.Examples include, but are not limited to, carboxymethyl, carboxyethyl,carboxyphenyl, and the like. An alkyl or phenyl group may be substitutedor unsubstituted.

As used herein, “alkylamino” means a radical —NHR or —NR₂ where each Ris, independently, an alkyl group. Examples include, but are not limitedto, methylamino, (1-methylethyl)amino, dimethyl amino, methylethylamino,di(1-methylethyl)amino, and the like. An alkylamino may be substitutedor unsubstituted.

As used herein, “hydroxyalkyl” means an alkyl group substituted with oneor more hydroxy groups. Representative examples include, but are notlimited to, hydroxymethyl, 2-hydroxyethyl; 2-hydroxypropyl;3-hydroxypropyl; 1-(hydroxymethyl)-2-methylpropyl; 2-hydroxybutyl;3-hydroxybutyl; 4-hydroxybutyl; 2,3-dihydroxypropyl;2-hydroxy-1-hydroxymethylethyl; 2,3-dihydroxybutyl; 3,4-dihydroxybutyland 2-(hydroxymethyl)-3-hydroxy-propyl; preferably 2-hydroxyethyl;2,3-dihydroxypropyl and 1-(hydroxymethyl) 2-hydroxyethyl. A hydroxyalkylmay be substituted or unsubstituted.

As used herein, “alkenyl” refers to a straight or branched hydrocarbonchain containing one or more double bonds. Although the presentdefinition covers the occurrence of the term “alkenyl” where nonumerical range is designated, the alkenyl group may have at least 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbonatoms, or any number in between. For example, the alkenyl group may bedesignated as “C₂₋₄ alkenyl,” “C₂₋₁₀ alkenyl,” “C₂₋₂₀ alkenyl” orsimilar designations. By way of example only, “C₂₋₄ alkenyl” indicatesthat there are two to four carbon atoms in the alkenyl chain, i.e., thealkenyl chain is selected from ethenyl; propen-1-yl; propen-2-yl;propen-3-yl; buten-1-yl; buten-2-yl; buten-3-yl; buten-4-yl;1-methyl-propen-1-yl; 2-methyl-propen-1-yl; 1-ethyl-ethen-1-yl;2-methyl-propen-3-yl; buta-1,3-dienyl; buta-1,2,-dienyl andbuta-1,2-dien-4-yl. Typical alkenyl groups include, but are in no waylimited to, ethenyl, propenyl, butenyl, pentenyl, and hexenyl, and thelike.

As used herein, “alkynyl” refers to a straight or branched hydrocarbonchain comprising one or more triple bonds. Although the presentdefinition covers the occurrence of the term “alkynyl” where nonumerical range is designated, the alkynyl group may have at least 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbonatoms, or any number in between. For example, the alkynyl group may bedesignated as “C₂₋₄ alkynyl” “C₂₋₁₀ alkynyl” “C₂₋₂₀ alkynyl” or similardesignations. By way of example only, “C₂₋₄ alkynyl” indicates thatthere are two to four carbon atoms in the alkynyl chain, e.g., thealkynyl chain is selected from ethynyl, propyn-1-yl, propyn-2-yl,butyn-1-yl, butyn-3-yl, butyn-4-yl, and 2-butynyl. Typical alkynylgroups include, but are in no way limited to, ethynyl, propynyl,butynyl, pentynyl, and hexynyl, and the like.

As used herein, “cycloalkyl” means a fully saturated carbocyclic ringradical or ring system. Examples include, but are not limited to,cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

As used herein, “aryl” refers to a carbocyclic (all carbon) monocyclicor multicyclic aromatic ring system (including fused ring systems wheretwo carbocyclic rings share a chemical bond). The number of carbon atomsin an aryl group can vary. For example, the aryl group can be a C₆-C₁₄aryl group, a C₆-C₁₀ aryl group, or a C₆ aryl group. Examples of arylgroups include, but are not limited to, phenyl, benzyl, α-naphthyl,β-naphthyl, biphenyl, anthryl, tetrahydronaphthyl, fluorenyl, indanyl,biphenyl enyl, and acenaphthenyl. Preferred aryl groups are phenyl andnaphthyl.

As used herein, “heteroaryl” refers to an aromatic ring or ring system(i.e., two or more fused rings that share two adjacent atoms) thatcomprise(s) one or more heteroatoms, that is, an element other thancarbon, including but not limited to, nitrogen, oxygen and sulfur, inthe ring backbone. When the heteroaryl is a ring system, every ring inthe system is aromatic. The heteroaryl group may have 5-18 ring members(i.e., the number of atoms making up the ring backbone, including carbonatoms and heteroatoms), although the present definition also covers theoccurrence of the term “heteroaryl” where no numerical range isdesignated. Examples of heteroaryl rings include, but are not limitedto, furyl, thienyl, phthalazinyl, pyrrolyl, oxazolyl, thiazolyl,imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, triazolyl,thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl,quinolinyl, isoquinlinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl,indolyl, isoindolyl, and benzothienyl.

As used herein, “haloalkyl” refers to an alkyl group, in which one ormore of the hydrogen atoms are replaced by a halogen (e.g.,mono-haloalkyl, di-haloalkyl and tri-haloalkyl). Such groups include butare not limited to, chloromethyl, fluoromethyl, difluoromethyl,trifluoromethyl and 1-chloro-2-fluoromethyl, 2-fluoroisobutyl. Ahaloalkyl may be substituted or unsubstituted.

As used herein, a “substituted” group may be substituted with one ormore group(s) individually and independently selected from alkyl,alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, benzyl,substituted benzyl, aryl, heteroaryl, heteroalicyclyl, aralkyl,heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxyl,alkoxy, aryloxy, acyl, mercapto, alkylthio, arylthio, cyano, halogen,thiol, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido,C-carboxy, protected C-carboxy, O-carboxy, isocyanato, thiocyanato,isothiocyanato, nitro, silyl, sulfenyl, sulfonyl, sulfonyl, haloalkyl,haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, an amino,a mono-substituted amino group and a di-substituted amino group, andprotected derivatives thereof.

As used herein, “halogen” refers to an atom of fluorine, chlorine,bromine or iodine.

As used herein, “homocyclic ring” refers to cycloalkyl or aryl.

As used herein, “heterocyclic ring” refers to a ring, which may contain1 to 4 hetero-atoms selected from among nitrogen, oxygen, sulfur andother atoms in addition to carbon atoms.

As used herein, the term “alcohol” is art-recognized and refers to anysubstance having an OH group attached to a carbon. In certainembodiments, the alcohol is a primary alcohol, a secondary alcohol, or atertiary alcohol. In some embodiments, the alcohol is a monohydricalcohol or a polyhydric alcohol. In certain embodiments, the alcohol isa diol, triol, tetraol, pentol, or hexol. In one embodiment, the alcoholis an aliphatic alcohol including saturated aliphatic or unsaturatedaliphatic alcohol. In some embodiments, the alcohol is an allylic,homoallylic, doubly allylic, doubly homoallylic, propargylic,homopropargylic, doubly propargylic, doubly homopropargylic, benzylic,homobenzylic, doubly benzylic, or doubly homobenzylic alcohol. Incertain embodiments, the alcohol is a glycol, a glycerol, an erythritol,a xylitol, a mannitol, an inositol, a menthol or a naturally ornon-naturally occurring sugar. In other embodiments, the alcohol is acycloalkanol, a phenol or other aryl alcohol, or a heteroaryl alcohol.Any of the aforementioned alcohols may be optionally substituted withone or more halogens, alkyls, alkenyls, alkynyls, hydroxyls, aminos,nitros, thiols, amines, imines, amides, phosphonates, phosphines,carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls,selenoethers, ketones, aldehydes, esters, fluoroalkyls, trifluoromethyl,and cyano groups. Examples include, but are not limited to, methanol,ethanol, isopropyl alcohol, butyl alcohol, isobutyl alcohol, t-butanol,pentanol, pentan-2-ol, pentan-3-ol, hexanol, heptanol, octanol,cyclopentanol, cyclohexanol, benzyl alcohol, 2-phenylethan-1-ol,2-phenylpropan-2-ol, 5-phenyl-pent-1-ol, 2,2,2-trifluoroethan-1-ol,2-methoxyethan-1-ol and the like.

As used herein, the singular forms “a,” “an,” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. Furthermore, to the extent that the terms “including,”“includes,” “having,” “has,” “with,” or variants thereof are used ineither the detailed description and/or the claims, such terms areintended to be inclusive in a manner similar to the term “comprising.”The transitional terms/phrases (and any grammatical variations thereof)“comprising,” “comprises,” and “comprise” can be used interchangeably;“consisting essentially of,” and “consists essentially of” can be usedinterchangeably; and “consisting,” and “consists” can be usedinterchangeably.

The transitional term “comprising,” “comprises,” or “comprise” isinclusive or open-ended and does not exclude additional, unrecitedelements or method steps. By contrast, the transitional phrase“consisting of” excludes any element, step, or ingredient not specifiedin the claim. The phrases “consisting” or “consists essentially of”indicate that the claim encompasses embodiments containing the specifiedmaterials or steps and those that do not materially affect the basic andnovel characteristic(s) of the claim. Use of the term “comprising”contemplates other embodiments that “consist” or “consisting essentiallyof” the recited component(s).

The term “about” or “approximately” means within an acceptable errorrange for the particular value as determined by one of ordinary skill inthe art, which will depend in part on how the value is measured ordetermined, i.e., the limitations of the measurement system. Forexample, “about” can mean within 1 or more than 1 standard deviation,per the practice in the art. Alternatively, “about” can mean a range ofup to 0-20%, 0 to 10%, 0 to 5%, or up to 1% of a given value. Whereparticular values are described in the application and claims, unlessotherwise stated the term “about” meaning within an acceptable errorrange for the particular value should be assumed.

Dinuclear Copper Catalyst

In one embodiment, the subject invention provides a dinuclear coppercatalyst that performs oxidation reactions—either oxygenation ordehydrogenation reactions—of various substrates containing C—H bonds,e.g., hydrocarbons. In one embodiment, the dinuclear copper catalystcomprises a dinuclear copper complex, i.e., dinuclear Cu(I)/Cu(II)complex, comprising a copper-containing compound having a bi-coppercenter joined by one or more bidentate or multidentate ligands.

The dinuclear Cu(I)/Cu(II) complex can cycle between the resting Cu(I)₂state, i.e., the dinuclear Cu(I) complex, and the catalytically activeor oxidized Cu(II)₂ form, i.e., the dinuclear Cu(II) complex. Thedinuclear Cu(I) complexes convert to the dinuclear Cu(II) complex uponexposure to, for example, atmospheric oxygen, and peroxides. Forexample, in the presence of O₂, the dinuclear Cu(I) complexes isoxidized to the dinuclear Cu(II) complex comprising a μ-OH at thebi-copper center, wherein the μ-OH can form a hydrogen bond with acounterion, such as an ionic ligand, stabilizing the dinuclear Cu(II)complex. The dinuclear Cu(II) complex returns to the resting Cu(I)₂state, i.e., the dinuclear Cu(I) complex upon reacting with a substratecomprising at least one reactive C—H bonds, e.g., hydrocarbons, byeither dehydrogenating the substrate with formation of H₂O, oroxygenating the substrate by adding its O-atom to the substrate.

In one embodiment, the dinuclear copper complex comprises a dinuclearcopper compound and a stabilizing ligand, wherein when the dinuclearcopper compound is at the resting state, i.e., being the dinuclear Cu(I)species, the stabilizing ligand stays neutral; and when the dinuclearcopper compound is at the oxidized state, i.e., being the dinuclearCu(II) species, the stabilizing ligand is ionic and can form a hydrogenbond with a μ-OH at the bi-copper center of the dinuclear Cu(II)species. The stabilization of the dinuclear Cu(II) species by ahydrogen-bonded stabilizing ligand ion is a key factor of the catalyticperformance of the dinuclear copper catalyst.

In one embodiment, the dinuclear Cu(I) compound/species/complex has ageneral structure of the formula (A):

wherein

represents a peripheral chelating ligand substitution, preferably,

is

and wherein R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″, R₃″, R₄″, R₅″,R₆″, R₂′″, R₃′″, R₄′″, R₅″′, and R₆″′ are each independently selectedfrom the group consisting of hydrogen, —COOH, —NO₂, alkyl, substitutedalkyl, aryl, substituted aryl, heteroalkyl, substituted heteroalkyl,heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl,heterocycloalkyl, substituted heterocycloalkyl, cycloalkenyl,substituted cycloalkenyl, alkenyl, substituted alkenyl, alkynyl, alkoxy,substituted alkoxy, acyl, carboxyalkyl, halogen, amino, substitutedamino, hydroxyl, hydroxylalkyl, and substituted hydroxylalkyl.

In a further embodiment, R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″,R₃″, R₄″, R₅″, R₆″, R₂′″, R₃′″, R₄′″, R₅″′, and R₆″′ are eachindependently selected from the group consisting of hydrogen, —COOH,—NO₂, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy,substituted alkoxy, acyl, carboxyalkyl, halogen, amino, substitutedamino, hydroxyl, and hydroxylalkyl.

In a preferred embodiment, R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″,R₃″, R₄″, R₅″, R₆″, R₂′″, R₃′″, R₄′″, R₅″′, and R₆″′ are eachindependently selected from the group consisting of hydrogen, —NO₂,alkyl, alkoxy, halogen, amino, and hydroxyl.

In specific embodiments, at least one of R₁, R₃, R₄, R₅, R₆, R₃′, R₄′,R₅′, R₆′, R₂″, R₃″, R₄″, R₅″, R₆″, R₂′″, R₃′″, R₄′″, R₅″′, and R₆″′ is—NO₂.

In a specific embodiment, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, and R₆′ areeach independently selected from the group consisting of hydrogen, F,Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In a specific embodiment, the dinuclear Cu(I) compound/species/complexhas a structure of:

wherein

is

and wherein R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, and R₆′ are eachindependently selected from the group consisting of hydrogen, F, Cl, Br,I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₃′, R₄′, and R₅′, are eachhydrogen; and R₆, and R₆′ are each independently selected from the groupconsisting of F, Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₆, R₃′, R₄′, and R₆′, are eachhydrogen; and R₅, and R₅′ are each independently selected from the groupconsisting of F, Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₅, R₆, R₃′, R₅′ and R₆′ are each hydrogen;and R₄, and R₄′ are each independently selected from the groupconsisting of F, Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₄, R₅, R₆, R₄′, R₅′ and R₆′ are each hydrogen;and R₃ and R₃′ are each independently selected from the group consistingof F, Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₆, R₄′, R₅′ and R₆′ are eachhydrogen; and R₃′ is selected from the group consisting of F, Cl, Br, I,Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₆, R₃′, R₅′ and R₆′ are eachhydrogen; and R₄′ is selected from the group consisting of F, Cl, Br, I,Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₆, R₃′, R₄′, and R₆′ are eachhydrogen; and R₅′ is selected from the group consisting of F, Cl, Br, I,Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₆, R₃′, R₄′, and R₅′ are eachhydrogen; and R₆′ is selected from the group consisting of F, Cl, Br, I,Me, CF₃, OMe, and tert-Bu.

In a specific embodiment,

is

In a specific embodiment, R₁, R₂″, R₄″, R₂′″, R₆″, R₄″′, and R₆″′ cannotall be —NO₂ at the same time.

In one embodiment, the dinuclear Cu(II) compound/species/complex has ageneral structure of the formula (B):

wherein

represents a peripheral chelating ligand substitution, preferably,

is

and wherein R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″, R₃″, R₄″, R₅″,R₆″, R₂′″, R₃′″, R₄′″, R₅″′, and R₆′″ are each independently selectedfrom the group consisting of hydrogen, —COOH, —NO₂, alkyl, substitutedalkyl, aryl, substituted aryl, heteroalkyl, substituted heteroalkyl,heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl,heterocycloalkyl, substituted heterocycloalkyl, cycloalkenyl,substituted cycloalkenyl, alkenyl, substituted alkenyl, alkynyl, alkoxy,substituted alkoxy, acyl, carboxyalkyl, halogen, amino, substitutedamino, hydroxyl, hydroxylalkyl, and substituted hydroxylalkyl.

In a further embodiment, R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″,R₃″, R₄″, R₅″, R₆″, R₂′″, R₃′″, R₄′″, R₅″′, and R₆″′ are eachindependently selected from the group consisting of hydrogen, —COOH,—NO₂, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy,substituted alkoxy, acyl, carboxyalkyl, halogen, amino, substitutedamino, hydroxyl, and hydroxylalkyl.

In a preferred embodiment, R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″,R₃″, R₄′, R₅″, R₆″, R₂″′, R₃′″, R₄″′, R₅″′, and R₆″′ are eachindependently selected from the group consisting of hydrogen, —NO₂,alkyl, alkoxy, halogen, amino, and hydroxyl.

In specific embodiments, at least one of R₁, R₃, R₄, R₅, R₆, R₃′, R₄′,R₅′, R₆′, R₂″, R₃″, R₄″, R₅″, R₆″, R₂′″, R₃′″, R₄′″, R₅′″, and R₆′″ is—NO₂.

In a specific embodiment, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, and R₆′ areeach independently selected from the group consisting of hydrogen, F,Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In a specific embodiment, the dinuclear Cu(II) compound/species/complexhas a structure of:

wherein

is

and wherein R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, and R₆′ are eachindependently selected from the group consisting of hydrogen, F, Cl, Br,I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₃′, R₄′, and R₅′, are eachhydrogen; and R₆, and R₆′ are each independently selected from the groupconsisting of F, Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₆, R₃′, R₄′, and R₆′, are eachhydrogen; and R₅, and R₅′ are each independently selected from the groupconsisting of F, Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₅, R₆, R₃′, R₅′ and R₆′ are each hydrogen;and R₄, and R₄′ are each independently selected from the groupconsisting of F, Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₄, R₅, R₆, R₄′, R₅′ and R₆′ are each hydrogen;and R₃ and R₃′ are each independently selected from the group consistingof F, Cl, Br, I, Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₆, R₄′, R₅′ and R₆′ are eachhydrogen; and R₃′ is selected from the group consisting of F, Cl, Br, I,Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₆, R₃′, R₅′ and R₆′ are eachhydrogen; and R₄′ is selected from the group consisting of F, Cl, Br, I,Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₆, R₃′, R₄′, and R₆′ are eachhydrogen; and R₅′ is selected from the group consisting of F, Cl, Br, I,Me, CF₃, OMe, and tert-Bu.

In specific embodiments, R₃, R₄, R₅, R₆, R₃′, R₄′, and R₅′ are eachhydrogen; and R₆′ is selected from the group consisting of F, Cl, Br, I,Me, CF₃, OMe, and tert-Bu.

In a specific embodiment, is

is

In a specific embodiment, R₁, R₂″, R₄″, R₂′″, R₆″, R₄″′, and R₆″′ cannotall be —NO₂ at the same time.

In one embodiment, the dinuclear copper catalyst comprises a stabilizingfree ligand as counterion, whose ionic form has a general structure of

that can form a hydrogen bond with the μ-OH of the dinuclear Cu(II)complex, while the neutral form of the free ligand has a generalstructure of

wherein R₁, R₂″, R₃″, R₄″, R₅″, R₆″, R₂″′, R₃′″, R₅″′, and R₆″′ are eachindependently selected from the group consisting of hydrogen, —COOH,—NO₂, alkyl, substituted alkyl, aryl, substituted aryl, heteroalkyl,substituted heteroalkyl, heteroaryl, substituted heteroaryl, cycloalkyl,substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl,cycloalkenyl, substituted cycloalkenyl, alkenyl, substituted alkenyl,alkynyl, alkoxy, substituted alkoxy, acyl, carboxyalkyl, halogen, amino,substituted amino, hydroxyl, hydroxylalkyl, and substitutedhydroxylalkyl.

In one embodiment, the dinuclear copper complex comprises a stabilizingligand or counter ion that can be the same or different from thebidentate or multidentate ligand of the dinuclear copper compound.

In a further embodiment, R₁, R₂″, R₃″, R₄″, R₅″, R₆″, R₂′″, R₃′″, R₄′″,R₅″′, and R₆′″ are each independently selected from the group consistingof hydrogen, —COOH, —NO₂, alkyl, substituted alkyl, alkenyl, substitutedalkenyl, alkoxy, substituted alkoxy, acyl, carboxyalkyl, halogen, amino,substituted amino, hydroxyl, and hydroxylalkyl.

In a preferred embodiment, R₁, R₂″, R₃″, R₄″, R₅″, R₆″, R₂′″, R₃′″,R₄′″, R₅′″, and R₆′″ are each independently selected from the groupconsisting of hydrogen, —NO₂, alkyl, alkoxy, halogen, amino, andhydroxyl. In a specific embodiment, at least one of R₁, R₂″, R₃″, R₄″,R₅″, R₆″, R₂′″, R₄″′, R₅″′, and R₆″′ is —NO₂. In a specific embodiment,R₁, R₂″, R₄″, R₂″′, and R₄″′ cannot all be —NO₂ at the same time.

In a specific embodiment, the stabilizing ligand comprises a stericallybulk poly-nitro pyrazolato ligand, for example, a pyrazolate, e.g.,3,5-bis(2,4-dinitrophenyl)-4-nitro-pyrazolate (pnpz-). Preferably, thestabilizing agent has a structure of

while the ionic form of the stabilizing ligand has a general structureof

In a specific embodiment, the copper catalyst is[{(η²-2,2′-bipy)Cu^(II)(μ-pnpz)}₂(μ-OH)](pnpz).

In a specific embodiment, the copper catalyst cannot be[{(η²-2,2′-bipy)Cu^(II)(μ-pnpz)}₂(μ-OH)](pnpz).

In one embodiment, the interconversion of the dinuclear copper speciesand the catalytic reaction may be represented, for example, by Scheme 1:

wherein L is the stabilizing ligand, and - - - represents the hydrogenbond between μ-OH and the stabilizing ligand.

The advantages of the dinuclear copper catalyst include: 1) it comprisesearth abundant metal copper, which is cost-effective and sustainable; 2)atmospheric oxygen can be used as oxidant to oxidize the Cu(I)—Cu(I)resting state of the complex to a Cu(II)—OH—Cu(II) species; 3) ligandsof the complex are readily available; 4) the properties of the catalystcan be tuned via judicious peripheral ligand substitution and theperipheral ligand substitution can produce catalysts tailored tospecific applications; and 5) the catalyst is easy to prepare underambient conditions; no inert atmosphere, and special instrumentationsare required.

In one embodiment, the subject invention provides a method forsynthesizing the dinuclear copper catalyst, the method comprising mixinga Cu(II) starting material, and one or more didentate or multidentateligands in a solvent. In a preferred embodiment, the Cu(II) startingmaterial comprises Cu(OH)₂. In a specific embodiment, the Cu(II)starting material is, for example, Cu(OH)₂. In a preferred embodiment,the method comprises mixing a Cu(II) starting material with one or moredidentate ligands, for example, 2,2′-bipyridine (bipy) and3,5-bis(2,4-dinitrophenyl)-4-nitro-pyrazole (pentanitropyrazole, pnpzH).

In one embodiment, the subject invention also provides compositionscomprising the dinuclear copper catalyst, or dinuclear copper complexes.In a specific embodiment, the dinuclear copper catalyst comprises amixture of the dinuclear Cu(I) complex and the dinuclear Cu(II) complex.In a specific embodiment, the dinuclear copper catalyst comprises puredinuclear Cu(II) complex. In one embodiment, the composition furthercomprises a carrier, or solvent.

Examples of the carrier include, but not limited to, aqueous vehicles,water-miscible vehicles, non-aqueous vehicles, stabilizers, solubilityenhancers, isotonic agents, buffering agents, suspending and dispersingagents, wetting or emulsifying agents, complexing agents, sequesteringor chelating agents, cryoprotectants, lyoprotectants, thickening agents,pH adjusting agents, and inert gases. Other suitable excipients orcarriers include, but are not limited to, dextran, glucose, maltose,sorbitol, xylitol, fructose, sucrose, and trehalose.

Examples of the solvent include, but are not limited to butyl acetate,tert-butylmethyl ether, dimethyl sulfoxide, ethyl acetate, ethylformate, heptane, isobutyl acetate, isopropyl acetate, methyl acetate,methylethyl ketone, methyl-isobutyl ketone, pentane, hexane, propylacetate, MeCN, EtCN, PrCN, and supercritical CO₂. In a specificembodiment, the solvent comprises MeCN.

Method of Use

In one embodiment, the subject invention provides a method for using thecatalyst of the subject invention to oxidize C—H bonds to form C—OHand/or C═C bonds, to oxidize C—OH bonds to C═O bonds, and/or to oxidizeand cleave C—C bonds in a substate. The methods involve the combinationof a substrate comprising one or more of reactive C—H, C—OH, and/or C—Cbonds, and a catalyst of the subject invention under, for example,ambient conditions. The methods are useful for the formation of, forexample, alkenes, alcohols, aldehyde, ketones and/or aromatic rings.Advantageously, the methods of the subject invention minimize reactionsteps, the handling of oxidized intermediates, and environmental impact.

In certain embodiments, the substrate is a DHA, toluene,2,2,4-trimethylpentane, methylcyclohexane, methane, cyclopropane,cyclobutane, cyclopentane, cyclohexane, indane, 2-oxoindane, thiophene,thianthrene, furan, pyran, isobenzofuran, chromene, xanthene,phenoxanthene, pyrrole, imidazole, pyrazole, isothiazole, isoxazole,pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole,indole, indazole, purine, quinolizine, isoquinoline, quinoline,phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline,pteridine, carbazole, carboline, phenanthridine, acridine, pyrimidine,phenanthroline, phenazine, phenarsazine, phenothiazine, furazan,phenoxazine, pyrrolidine, oxolane, thiolane, oxazole, piperidine,piperazine, morpholine, lactone, lactam, azetidinone, pyrrolidinone,sultam, or sultone; and the substrate is optionally substituted withhalogens, alkyls, alkenyls, alkynyls, hydroxyls, aminos, nitros, thiols,amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls,silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes,esters, fluoroalkyls, trifluoromethyl, or cyano.

In certain embodiments, the methods for synthesizing alkenes and/oralcohols use, for example, hydrocarbons as substrates viacopper-mediated C—H oxygenation to form C—OH or via copper-mediated C—Hdehydrogenation to form C═C.

In one embodiment, the methods for synthesizing aldehyde and/or ketonesuses, for example, alcohols, as substrates via copper-mediateddehydrogenation of C—OH to form a C═O and/or CHO group.

In one embodiment, the subject invention provides a method ofcopper-mediated oxidization and cleavage of one or more C—C bonds of asubstrate. Preferably, the C—C bond is the one adjacent to a C═O group,i.e., C—C═O.

In one embodiment, the subject invention provides a method forcatalyzing or oxidizing a substrate (e.g., hydrocarbon) comprising atleast one reactive C—H bond, the method comprising contacting thesubstrate (e.g., hydrocarbon) with the dinuclear copper catalyst of thesubject invention, thereby forming a oxidized product comprising atleast one C—OH by adding the O atom of the dinuclear Cu(II) species toC—H bonds, and/or at least one C═C bond by dehydrogenating from the C—Hbonds.

In one embodiment, the subject invention provides a method forcatalyzing or oxidizing a substrate comprising at least a reactive C—OHbond, the method comprising contacting, combining, and/or mixing thesubstrate with the dinuclear copper catalyst of the subject invention,thereby forming a oxidized product comprising at least one C═O bond.

In one embodiment, the subject invention provides a method forcatalyzing or oxidizing an alcohol, the method comprising contacting,combining, and/or mixing the alcohol with the dinuclear copper catalystof the subject invention.

In one embodiment, the subject invention provides a method for producingan alcohol, the method comprising contacting, combining, and/or mixing asubstrate (e.g., hydrocarbon) with the dinuclear copper catalyst of thesubject invention, the substrate (e.g., hydrocarbon) comprising at leastone reactive C—H bond.

In one embodiment, the subject invention provides a method for producingan alkene, the method comprising contacting, combining, and/or mixing asubstrate (e.g., hydrocarbon) with the dinuclear copper catalyst of thesubject invention, the substrate (e.g., hydrocarbon) comprising at leastone reactive C—H bond.

In one embodiment, the subject invention provides a method for producingan aromatic ring, the method comprising contacting, combining, and/ormixing a substrate (e.g., hydrocarbon) with the dinuclear coppercatalyst of the subject invention, the substrate (e.g., hydrocarbon)comprising at least one reactive C—H bond. Preferably, the substrate isa hydrocarbon comprising one or more 5, and/or 6 membered rings.

In one embodiment, the subject invention provides a method for producingan aldehyde, the method comprising contacting, combining, and/or mixinga substrate (e.g., hydrocarbon) with the dinuclear copper catalyst ofthe subject invention, the substrate (e.g., hydrocarbon) comprising atleast one reactive C—H bond. In certain embodiments, producing analdehyde may comprise a series of catalytic reactions including, forexample, a step of producing an alcohol from the reaction between thesubstrate (e.g., hydrocarbon) and the dinuclear copper catalyst, and astep of producing the aldehyde from the reaction between the alcohol andthe dinuclear copper catalyst.

In one embodiment, the subject invention provides a method for producinga ketone, the method comprising contacting a substrate (e.g.,hydrocarbon) with the dinuclear copper catalyst of the subjectinvention, the substrate (e.g., hydrocarbon) comprising at least onereactive C—H bond. In certain embodiments, producing a ketone maycomprise a series of catalytic reactions including, for example, a stepof producing an alcohol from the reaction between the substrate (e.g.,hydrocarbon) and the dinuclear copper catalyst, and a step of producingthe ketone from the reaction between the alcohol and the dinuclearcopper catalyst.

In certain embodiments, the subject invention provides methods foroxidizing a substrate by using the dinuclear copper catalyst of thesubject invention, the methods comprising one or more of the followingoxidization steps:

1) oxygenating one or more C—H bonds of the substrate, e.g.,hydrocarbon, to form one or more C—OH bonds;

2) dehydrogenating one or more C—H bonds of the substrate to form one ormore C═C bonds, preferably, the substrate having one or more ringstructures, more preferably, one or more C—H bonds being in 5- and/or6-membered rings;

3) oxidizing one or more C—OH bonds of the substrate, e.g., hydrocarbon,to form one or more C═O bonds; and

4) oxidizing and cleaving one or more C—C bonds of the substrate tobreak the bonding of such two carbons, preferably, the C—C bond isadjacent to a C═O group. For example, the substrate comprises one ormore C—C═O groups.

In one embodiment, the substrate has a C—H bond energy of at least 300kJ/mol, at least 310 kJ/mol, at least 320 kJ/mol, at least 330 kJ/mol,at least 340 kJ/mol, at least 350 kJ/mol, at least 360 kJ/mol, at least370 kJ/mol, at least 380 kJ/mol, at least 390 kJ/mol, at least 400kJ/mol, at least 410 kJ/mol, at least 420 kJ/mol, at least 430 kJ/mol,at least 440 kJ/mol, or any in between. In some embodiments, thesubstrate has a C—H bond energy of, for example, at least 364 kJ/mol, atleast 365 kJ/mol, at least 384 kJ/mol, at least 418 kJ/mol, or at least439 kJ/mol.

In one embodiment, the catalytic reaction occurs with atmosphericoxygen. Preferably, the catalytic reaction occurs in the presence ofpure O₂. The catalytic reaction performs better with pure O₂ than withambient air (atmospheric oxygen).

In one embodiment, the methods of the subject invention comprise a stepof identifying or detecting the product including intermediate productand/or final product of the catalytic reaction by methods known in theart, for example, GC-MS, UV-Vis, NMR and/or X-ray crystallography.

In one embodiment, the method of the subject invention may furthercomprise a step of determining whether the oxygen is limited and thecatalytic reaction is terminated, wherein a color change in the mixtureof the substrate and the dinuclear copper catalyst from green tored/orange/brown is indicative that the oxygen is limited and thecatalytic reaction is terminated.

In one embodiment, the subject invention also provides a method forrecovering the resting dinuclear copper catalyst, the method comprisingmixing the dinuclear copper catalyst with a substrate in a closedcontainer, and recovering the dinuclear copper catalyst at the restingstate when a color change in the mixture from green to red/orange/brownoccurs.

In one embodiment, the reaction in the methods of the subject inventiontakes place in a solvent. Examples of the solvent include, but are notlimited to, acetic acid, acetone, anisole, 1-butanol, 2-butanol, butylacetate, tert-butylmethyl ether, cumene, dimethyl sulfoxide, ethanol,ethyl acetate, ethyl ether, ethyl formate, formic acid, heptane,isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol,methylethyl ketone, methyl-isobutyl ketone, 2-methyl-1-propanol,pentane, 1-pentanol, 1-propanol, 2-propanol and propyl acetate. In aspecific embodiment, the solvent comprises MeCN.

In one embodiment, the reaction in the methods of the subject inventionmay run at a temperature ranging from about 4° C. to about 100° C., fromabout 10° C. to about 90° C., from about 20° C. to about 80° C., fromabout 20° C. to about 70° C., from about 20° C. to about 60° C., fromabout 20° C. to about 50° C., from about 20° C. to about 40° C., fromabout 20° C. to about 30° C., from about 30° C. to about 70° C., fromabout 30° C. to about 50° C., from about 40° C. to about 70° C., fromabout 40° C. to about 80° C., from about 50° C. to about 90° C., or fromabout 50° C. to about 100° C. Preferably, the reaction in the methods ofthe subject invention may run at room temperature.

The catalyst can be used in a wide range of amount in the reactionaccording to the subject invention. For example, the catalyst may bepresent in less than about 90 mol %, about 85 mol %, about 80 mol %,about 75 mol %, about 70 mol %, about 65 mol %, about 60 mol %, about 55mol %, about 50 mol %, about 45 mol %, about 40 mol %, about 35 mol %,about 30 mol %, about 25 mol %, about 20 mol %, about 15 mol %, about 10mol %, about 5 mol %, or about 1 mol %, relative to the substrate.

In one embodiment, the catalyst and the substrate in a reactionaccording to the subject invention may be loaded at a molar ratio of,for example, from 1:1 to 1:500, from 1:1 to 1:400, from 1:1 to 1:300,from 1:1 to 1:250, from 1:1 to 1:200, from 1:1 to 1:150, from 1:1 to1:100, from 1:1 to 1:90, from 1:1 to 1:80, from 1:1 to 1:70, from 1:1 to1:60, from 1:1 to 1:50, from 1:1 to 1:40, from 1:1 to 1:30, from 1:1 to1:20, from 1:1 to 1:10, or from 1:1 to 1:5.

In one embodiment, the reaction of the subject invention has a productyield of at least about 5%, at least about 10%, at least about 15%, atleast about 20%, at least about 25%, at least about 30%, at least about35%, at least about 40%, at least about 45, at least about 50%, at leastabout 55%, at least about 60%, at least about 65%, at least about 70%,at least about 75%, at least about 80%, at least about 85%, at leastabout 90%, at least about 95%, at least about 99%, or at least about99.5%. In a preferred embodiment, the reaction of the subject inventionhas a product yield of 99.9% or 100%.

When ranges are used herein, such as for dose ranges, combinations andsubcombinations of ranges (e.g., subranges within the disclosed range),specific embodiments therein are intended to be explicitly included.

Unless otherwise defined, all terms of art, notations and otherscientific terms or terminology used herein are intended to have themeanings commonly understood by those of skill in the art to which thisinvention pertains. In some cases, terms with commonly understoodmeanings are defined herein for clarity and/or for ready reference, andthe inclusion of such definitions herein should not necessarily beconstrued to represent a substantial difference over what is generallyunderstood in the art. It will be further understood that terms, such asthose defined in commonly used dictionaries, should be interpreted ashaving a meaning that is consistent with their meaning in the context ofthe relevant art and/or as otherwise defined herein.

EXAMPLES

The copper complexes described herein can be prepared under ambientconditions open to the atmosphere. The catalyst is easily synthesized ingood yield from a commercially available Cu(II) starting material,2,2′-bipyridine (bipy) and 3,5-bis(2,4-dinitrophenyl)-4-nitro-pyrazole(pentanitropyrazole, pnpzH). The Cu(II)₂(μ-OH) product,[{(η²-2,2′-bipy)Cu(II)(μ-pnpz)}₂(μ-OH)](pnpz), can be characterized byelemental analysis, mass spectroscopy and single crystal X-ray structuredetermination. The green crystalline solid cation crystallizes with apnpz anion H-bonded to the μ-OH group.

Reaction of Cu(OH)₂, pnpzH and 2,2′-bipy in acetonitrile yields the[{(η²-2,2′-bipy)Cu(II)(μ-pnpz)}₂(μ-OH)](pnpz) complex (Cu(II)₂), asfollows.

[{(η²-2,2′-bipy)Cu((II)(μ-pnpz)}₂(μ-OH)](pnpz): 25.6 mg (0.262 mmol)Cu(OH)₂ and 200 mg (0.397 mmol) pnpzH were stirred in 5 mL CH₃CN untilall solids were dissolved. To the resulting light blue solution, wasadded 41 mg (0.262 mmol) 2,2′-bipy, turning gradually the solution colorfrom light green to deep green over a period of 2 h. The green reactionmixture was filtered through Celite and was set to crystallize by slowdiethylether vapor diffusion, resulting in single crystals appropriatefor X-ray diffraction analysis; Yield, 288 mg (62%). ForC₆₅H₃₅N₂₅O₃₁Cu₂: Calc./Found %, C 43.63/43.47; H 1.97/1.89; N19.57/19.20. UV-Vis (nm, CH₃CN): 247, 304, 316(sh), 380.

X-ray structural determination, Cu^(II) ₂·x Solvent: C₆₅H₃₅Cu₂N₂₅O₃₁,M=1789.26, triclinic P-1, a=16.480(6) Å, b=16.668(6) Å, c=22.481(8) Å,α=76.090(9)°, β=74.621(9)°, γ=69.582(9)°, V=5505(3) Å³, Z=2, d=1.090g/cm³, R₁=5.34% and GoF=1.046 for 1124 parameters refined with 12559observed reflections.

The crystal structure of [{(η²-2,2′-bipy)Cu(II)(μ-pnpz)}₂(μ-OH)](pnpz)consists of a dinuclear copper molecule—Cu . . . Cu, 3.003 Å—heldtogether by two bridging pyrazolato ligands—Cu—N, 2.040-2.161 Å—and onebridging hydroxide—Cu—O, 1.912 and 1.931 Å (FIG. 1 ).

Example 1—Dicopper Complex Catalyzes dihydroanthracene to anthracene

Atmospheric dioxygen (O₂) can oxidize Cu(I)₂ to Cu(II)₂, and the lattercarries out oxidation reactions of hydrocarbon substrates, cyclingbetween Cu(I)₂ and Cu(II)₂ complexes. The reaction of Cu(II)₂(μ-OH) withdihydroanthracene (DHA) was investigated in MeCN. The result shows thatCu(II)₂(μ-OH) can catalyze DHA by dehydrogenating it to anthracene (FIG.2 ). DHA has a C—H bond energy of 326 kJ/mol. Under stoichiometricconditions, the reaction is easily followed spectroscopically, and alsoby visual inspection, because the green Cu(II)₂(μ-OH) turns into the redCu(I)₂, which was isolated and fully characterized. In a 1:100 molarratio of Cu(II)₂(μ-OH) to DHA reaction mixture, the reaction proceeds aslong as it remains open to the atmosphere. When the reaction is sealed,the green solution turns gradually to brownish-orange and the reactionsstops. Exposing this mixture again to the atmosphere, causes thecatalysts to turn to its original green color and the oxidation of DHArestarts.

The role of the H-bonded pnpz anion, which modifies the secondarycoordination sphere of the metal centers, is critical to the catalyticactivity: it shuttles the proton necessary for the formation of the μ-OHgroup, in a similar manner to the stabilization of Cu—OH moieties inmetalloproteins. The isolated Cu(I)₂ species, upon oxidation does notpossess the catalytic activity.

Example 2—Dicopper Complex Catalyzes toluene to benzyl Alcohol andbenzaldehyde

The catalytic oxidation of toluene (C—H bond energy, 364 kJ/mol) in MeCNwas investigated. The result shows that Cu(II)₂(μ-OH) can catalyzetoluene by oxygenating (i.e., adding the O-atom of μ-OH to thesubstrate) it to benzyl alcohol (FIG. 3 ), which can further becatalyzed by Cu(II)₂(μ-OH) to benzaldehyde. Thus, the catalytic reactionproduces a mixture of benzyl alcohol and benzaldehyde, which can beidentified by GC-MS.

Example 3—Dicopper Complex Catalyzes cyclohexane tocyclohexanone/cyclohexanol

The catalytic oxidation of cyclohexane (C—H bond energy, 418 kJ/mol) inMeCN produces a mixture of cyclohexanol, cyclohexanone and1,6-hexanediol, which can be identified by GC-MS. When the reaction iscarried out in tetrahydrofuran (thf; bond energy, 384 kJ/mol),1,4-butyrolactone is also found among the reaction products.

Example 4—Dicopper Complex Catalyzes 2,2,4-trimethylpentane,methylcyclohexane and methane

Dicopper complex is used to catalyze hydrocarbons with a higher C—H bondenergy, for example, 2,2,4-trimethylpentane (431 kJ/mol),methylcyclohexane (both 439 kJ/mol) and methane (439 kJ/mol).

All patents, patent applications, provisional applications, andpublications referred to or cited herein are incorporated by referencein their entirety, including all figures and tables, to the extent theyare not inconsistent with the explicit teachings of this specification.

It should be understood that the examples and embodiments describedherein are for illustrative purposes only and that various modificationsor changes in light thereof will be suggested to persons skilled in theart and are to be included within the spirit and purview of thisapplication and the scope of the appended claims. These examples shouldnot be construed as limiting. In addition, any elements or limitationsof any invention or embodiment thereof disclosed herein can be combinedwith any and/or all other elements or limitations (individually or inany combination) or any other invention or embodiment thereof disclosedherein, and all such combinations are contemplated within the scope ofthe invention without limitation thereto.

We claim:
 1. A dinuclear copper catalyst comprising a dinuclear Cu(II)complex and a stabilizing counter ion, the dinuclear Cu(II) complexhaving a general structure of formula (B):

wherein

is

and wherein R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″, R₃″, R₄″, R₅″,R₆″, R₂″′, R₃″′, R₄″′, R₅″′, and R₆″′ are each independently selectedfrom the group consisting of hydrogen, —NO₂, —OH, alkyl, substitutedalkyl, aryl, heteroalkyl, alkenyl, substituted alkenyl, alkoxy,substituted alkoxy, acyl, carboxyalkyl, halogen, and amino, wherein whenR₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, and R₆′ are hydrogen, R₁, R₂″, R₄″, R₆″,R₂″′, R₄″′, and R₆″′ are —NO₂.
 2. The dinuclear copper catalyst of claim1, wherein at least ten of R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″,R₃″, R₄″, R₅″, R₆″, R₂′″, R₃′″, R₄′″, R₅″′, and R₆′″ are —NO₂.
 3. Thedinuclear copper catalyst of claim 1, the stabilizing counter ion havinga general structure of:

wherein R₁, R₂″, R₃″, R₄″, R₅″, R₆″, R₂″′, R₃′″, R₄′″, R₅′″, and R₆′″are each independently selected from the group consisting of hydrogen,—NO₂, alkyl, substituted alkyl, alkoxy, halogen, amino, and hydroxyl,wherein when R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, and R₆′, are hydrogen, R₁,R₂″, R₄″, R₆″, R₂′″, R₄′″, and R₆′″ are —NO₂.
 4. The dinuclear coppercatalyst of claim 3, the stabilizing counter ion having a structure of:


5. The dinuclear copper catalyst of claim 3, the stabilizing counter ionhaving a general structure of:

wherein R₁, R₂″, R₄″, R₆″, R₂′″, R₄′″, and R₆′″ are —NO₂.
 6. Thedinuclear copper catalyst of claim 1, wherein R₃, R₄, R₅, R₆, R₃′, R₄′,R₅′, and R₆′ are each independently selected from the group consistingof hydrogen, F, CI, Br, I, Me, CF₃, OMe, and tert-Bu.
 7. The dinuclearcopper catalyst of claim 1, wherein R₁, R₂″, R₄″, R₆″, R₂′″, R₄′″, andR₆′″ are —NO₂.
 8. The dinuclear copper catalyst of claim 1, wherein R₃,R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₃″, R₅″, R₃′″, and R₅′″ are hydrogen,and R₁, R₂″, R₄″, R₆″, R₂′″, R₄′″, and R₆′″ are —NO₂.
 9. The dinuclearcopper catalyst of claim 1, wherein

is


10. The dinuclear copper catalyst of claim 1, wherein R₁, R₂″, R₃″, R₄″,R₅″, R₆″, R₂′″, R₃′″, R₄′″, R₅′″, and R₆′″ are —NO₂.
 11. The dinuclearcopper catalyst of claim 1, wherein the dinuclear Cu(II) complex can bereduced to a dinuclear Cu(I) complex having a general structure offormula (A):

wherein

is

and wherein R₁, R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, R₆′, R₂″, R₃″, R₄″, R₅″,R₆″, R₂′″, R₃′″, R₄′″, R₅′″, and R₆′″ are each independently selectedfrom the group consisting of hydrogen, —NO₂, —OH, alkyl, substitutedalkyl, aryl, heteroalkyl, alkenyl, substituted alkenyl, alkoxy,substituted alkoxy, acyl, carboxyalkyl, halogen, and amino, wherein whenR₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, and R₆′ are hydrogen, R₁, R₂″, R₄″, R₆″,R₂′″, R₄′″, and R₆′″ are —NO₂.
 12. The dinuclear copper catalyst ofclaim 11, wherein R₃, R₄, R₅, R₆, R₃′, R₄′, R₅′, and R₆′ are eachindependently selected from the group consisting of hydrogen, F, CI, Br,I, Me, CF₃, OMe, and tert-Bu.
 13. The dinuclear copper catalyst of claim11, wherein R₁, R₂″, R₄″, R₆″, R₂′″, R₄′″, and R₆′″ are —NO₂.
 14. Thedinuclear copper catalyst of claim 11, wherein R₃, R₄, R₅, R₆, R₃′, R₄′,R₅′, R₆′, R₃″, R₅″, R₃′″, and R₅′″ are hydrogen, and R₁, R₂″, R₄″, R₆″,R₂′″, R₄′″, and R₆′″ are —NO₂.
 15. The dinuclear copper catalyst ofclaim 11, wherein

is


16. The dinuclear copper catalyst of claim 11, wherein R₁, R₂″, R₃″,R₄″, R₅″, R₆″, R₂′″, R₃′″, R₄′″, R₅′″, and R₆′″ are —NO₂.
 17. Acomposition comprising the dinuclear copper catalyst of claim
 1. 18. Acomposition comprising the dinuclear copper catalyst of claim 11.